5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia
2003 | journal article. A publication with affiliation to the University of Göttingen.
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5-HT4(a) receptors avert opioid-induced breathing depression without loss of analgesia
Manzke, T.; Guenther, U.; Ponimaskin, E. G.; Haller, M.; Dutschmann, M.; Schwarzacher, S. & Richter, D. W. (2003)
Science, 301(5630) pp. 226-229. DOI: https://doi.org/10.1126/science.1084674
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Details
- Authors
- Manzke, Till; Guenther, U.; Ponimaskin, Evgeni G.; Haller, M.; Dutschmann, Mathias; Schwarzacher, S.; Richter, Diethelm W.
- Abstract
- Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT4(a)] receptors are strongly expressed in respiratory PBC neurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT4 receptor specific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3', 5'-monophosphate levels through the convergent signaling pathways in neurons.
- Issue Date
- 2003
- Status
- published
- Publisher
- Amer Assoc Advancement Science
- Journal
- Science
- ISSN
- 0036-8075